The syntheses and properties of tricyclic pyrrolo[2,3-d]pyrimidine analogues of S6-methylthioguanine and O6-methylguanine

Abstract

The syntheses of novel tricyclic pyrrolo[2,3-d]pyrimidine analogues of S⁶-methylthioguanine are described. The crystal structures and pK_a values of these and related O⁶-methylguanine analogues are reported. All compounds display higher pK_a values than O⁶-methylguanine with the sulfur-containing analogues being the more basic and exhibiting higher stability in aqueous solution. In a standard substrate assay with the human repair protein O⁶-methylguanine-DNA methyltransferase (MGMT) only the oxygen-containing analogue displayed activity.